Alcoholic Liver Disease

Alcoholic liver disease (ALD) has three stages: fatty liver, hepatitis and cirrhosis. Causes include damage of the liver cells by ethanol, acetaldehyde (a product of ethanol metabolism), free radicals (their creation is stimulated by ethanol), fat accumulated within the liver cells, and endotoxins from the alcohol-damaged intestine ^[1].

Risk factors for ALD include:

• Genetic predisposition, including hereditary hemochromatosis ^[1]
• Women are twice as susceptible for liver disease than men ^[1].
• Obesity ^[2]
• Heavy drinkers infected with hepatitis B (HBV) or C virus (HCV), or HBV carriers are at increased risk of developing liver cirrhosis or liver cancer ^[1,6,7].
• Protein deficiency and vitamin deficiencies ^[3,4]
• Drinking on an empty stomach more likely result in liver disease than drinking with meals ^[1].
• Acetaminophen (paracetamol) taken by chronic alcoholics may increase the risk of acute or chronic liver damage or worsen existing damage ^[8,9], but according to some studies, acetaminophen in the prescribed doses is safe for persons with liver disease ^[5].
• It is not clear if drinking spirits or beer more likely results in liver disease than drinking wine ^[1].

Alcoholic Fatty Liver

Alcoholic fatty liver is an accumulation of more than 5% fat within the liver cells due to alcohol-induced increased synthesis of the body fat. Fatty liver develops in about 90% chronic alcoholics, but sometimes even in healthy individuals after a single heavy drinking session ^[1,3]. Fatty liver usually causes no symptoms or signs, except occasional enlarged liver ^[1,10]. Fatty liver usually heals within 4-6 weeks after stopping or significantly reducing drinking, but in about 10% of individuals it may proceed to cirrhosis despite abstinence ^[1]. Treatment includes abstinence of alcohol and correction of eventual nutrient deficiencies ^[11].

Alcoholic Hepatitis

Alcoholic hepatitis is an inflammation of the liver that occurs in up to 35% men who drink three or more drinks per day or women who drink 1.5 or more drinks per day ^[1,3]. Symptoms may include enlarged liver, upper right abdominal tenderness or pain or, in more severe cases, loss of appetite, fatigue, fever, jaundice or accumulation of the fluid in the abdominal cavity) ascites ^[10]. Diagnosis is made  on the basis of alcohol drinking history and physical findings; laboratory findings are nonspecific and include elevated levels of liver enzymes and white blood cells ^[10].

In moderate or severe hepatitis, appropriate nutrition to correct nutrient deficiencies and protein-calorie malnutrition is usually needed ^[13]. After stopping drinking, alcoholic hepatitis resolves completely over several weeks to months in about 30% individuals, but with continuing drinking, up to 70% of affected individuals may develop cirrhosis ^[14]. One-year mortality in alcohol hepatitis is about 40% ^[15].

Alcoholic Liver Cirrhosis

Alcoholic liver cirrhosis is scarring of the liver due to overgrowth of the fibrous tissue that replaces the damaged liver cells. Liver cirrhosis does not heal even after stopping drinking ^[1].

Risk factors ^{[1, 16-p.160]}:

• Drinking more than 5 standard drinks per day for men or more than 1.5 per day drinks for women for 10 years or more increases the risk of cirrhosis by 6-41% (depending on the country).
• Drinking on an empty stomach
• Everyday drinking
• Smoking ^[17,18,19]

Symptoms. Individuals with early cirrhosis may have no symptoms and have normal blood tests. Otherwise, symptoms may include enlarged liver and, sometimes, spleen. Symptoms of advanced cirrhosis may include muscle wasting, weakness, anorexia, nausea, loss of weight and itching ^[20]. Liver is usually not enlarged and may be even smaller than normal, due to scarring.

Physical examination in alcoholic liver disease:

• Jaundice may develop in alcoholic hepatitis or advanced cirrhosis ^[20]
• Skin darkening (hyperpigmentation) around the eyes, mouth and on the legs may be present in cirrhosis ^[21].
• Spider-shaped veins on the face or chest (reddish or bluish spots, few millimeters in diameter, they blanch upon pressure) are caused by increased levels of estrogen in individuals with cirrhosis ^[21].
• Redness of the palms (palmar erythema), fibrous threads under the palm skin (Dupuytren’s contracture)
• An enlargement of the fingertips and bulging of the nails (finger clubbing), or flat or sunken nails, horizontal white and pink stripes under the nails ^[21]
• Liver may be enlarged in fatty liver (sometimes), alcoholic hepatitis and early stages of cirrhosis (in advanced stages it may be of normal or reduced size).
• Spleen may be enlarged in alcoholic hepatitis and advanced liver cirrhosis.

Complications of Alcoholic Liver Disease

• Porphyria cutanea tarda is a skin condition with erosions, blisters, hardening and increased hair grow on a sun-exposed skin (face and hands) ^[21].
• Painless enlargement of the parotid glands (below the ears) and tear glands (below the upper eyelids) is called sialadenosis ^[10,22].
• Visible veins on the abdomen (caput medusae)
• Leg swelling ^[20]
• Accumulation of the fluid in the abdominal cavity (ascites) with abdominal distension occurs due to narrowed blood vessels in the cirrhotic liver and subsequent increase of the pressure in the portal vein, and due to low blood albumin levels (hypoalbuminemia), which both result in the escape of the fluid from the intestinal veins.
• Esophageal varices–dilated and engorged veins protruding into the lumen of the esophagus–may develop in about 50% individuals with liver cirrhosis due to increased pressure in the portal vein ^[10]. Esophageal varices may rupture and cause bleeding, which may be fatal.
• Hemorrhoids due to increased pressure in the rectal veins ^[23]
• Easy bruising and bleeding due to decreased amount of clotting proteins (in cirrhosis) ^[20]
• Muscle wasting due to protein malabsorption, impaired protein synthesis in the liver and increased protein breakdown in the muscles (in cirrhosis) ^[24]
• Hepatic encephalopathy [hepatic = related to liver; encephalon = brain; -pathy = disease] is a worsening of brain function caused by ammonia that accumulates in the blood in individuals with severe alcoholic hepatitis or cirrhosis. Symptoms may include sleepiness, fatigue, confusion or coma ^[25]. About 80% of those who fall into a coma, die ^[26].
• Kidney enlargement ^[27]
• Hepato-renal syndrome, a kidney failure caused by liver failure ^[10]
• Gallstones ^[20]
• Diabetes type 2 ^[20]
• Liver cancer (hepatocellular carcinoma) may develop in about 3% of individuals with liver cirrhosis ^[24].

Diagnosis

Blood tests in liver cirrhosis may show ^[10]:

• Elevated liver enzymes (AST, ALT, GGT)
• Elevated white blood cells, low platelets
• Increased volume (MCV) of red blood cells (macrocytosis)
• Elevated uric acid and triglycerides, hyperglycemia, low levels of potassium and magnesium
• Markers of severe alcoholic hepatitis or cirrhosis: elevated bilirubin, prolonged clotting time (prothrombine time or PT), low albumins (hypoalbuminemia)

Other tests in alcoholic liver disease:

• Ultrasonography may reveal enlarged liver (in alcoholic hepatitis), fibrous tissue in cirrhosis, free fluid in the abdominal cavity in ascites, abnormal mass in liver cancer ^[12].
• Liver biopsy (taking a sample of the liver tissue by a needle inserted through the abdominal skin) and histological examination (investigating of the obtained sample under the microscope) may be performed to evaluate the severity of the liver disease.

Treatment and Prognosis

Treatment of alcoholic liver disease may include ^[3,4,10]:

• Loosing weight may help in treatment of alcoholic fatty liver.
• Alcohol abstinence may result in complete recovery of fatty liver and alcoholic hepatitis and improvement even in advanced cirrhosis ^[10].
• Stopping smoking may slow down the progression of cirrhosis.
• Nutritious diet (2,000-3,000 kcal/day, determined by a dietitian) may greatly increase survival and decrease hospitalizations in patients with severe alcoholic hepatitis or cirrhosis ^[10,28].
• Pentoxifylline increases survival in severe alcoholic hepatitis
• Steroids (prednisolone) should be reserved only for severe liver disease ^[10].
• Liver transplantation is an option in advanced alcoholic liver disease, usually in patients with terminal cirrhosis; it usually has good prognosis ^[1,10].

Drugs or supplements NOT proven to help in liver cirrhosis so far: anabolic steroids, calcium channel blockers, colchicine, metadoxine (an antioxidant), milk thistle (silymariyin), polyunsaturated lecithin (PPC), propylthiouracyl (PTU), S-adenosylmethionine (SAMe), saturated fat, vitamin E ^[1,3,10].

Prognosis of an alcoholic liver disease:

• Abstinence improves prognosis in all stages of alcoholic liver disease ^[1]. After stopping drinking, fatty liver is reversible in about 80% and alcoholic hepatitis in about 30% ^[14].
• In one study, from 1155 patients, 54% of patients with uncomplicated cirrhosis and 21% patients with advanced cirrhosis have survived for six years ^[2].